NEET MDS Lessons
Physiology
Red blood cell cycle:
RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. RBCs require Vitamin B12, folic acid, and iron. The lifespan of RBC averages 120 days. Aged and damaged red cells are disposed of in the spleen and liver by macrophages. The globin is digested and the amino acids released into the blood for protein manufacture; the heme is toxic and cannot be reused, so it is made into bilirubin and removed from the blood by the liver to be excreted in the bile. The red bile pigment bilirubin oxidizes into the green pigment biliverdin and together they give bile and feces their characteristic color. Iron is picked up by a globulin protein (apotransferrin) to be transported as transferrin and then stored, mostly in the liver, as hemosiderin or ferritin. Ferritin is short term iron storage in constant equilibrium with plasma iron carried by transferrin. Hemosiderin is long term iron storage, forming dense granules visible in liver and other cells which are difficult for the body to mobilize.
Some iron is lost from the blood due to hemorrhage, menstruation, etc. and must be replaced from the diet. On average men need to replace about 1 mg of iron per day, women need 2 mg. Apotransferrin (transferrin without the iron) is present in GI lining cells and is also released in the bile. It picks up iron from the GI tract and stimulates receptors on the lining cells which absorb it by pinocytosis. Once through the mucosal cell iron is carried in blood as transferrin to the liver and marrow. Iron leaves the transferrin molecule to bind to ferritin in these tissues. Most excess iron will not be absorbed due to saturation of ferritin, reduction of apotransferrin, and an inhibitory process in the lining tissue.
Erythropoietin Mechanism:
Myeloid (blood producing) tissue is found in the red bone marrow located in the spongy bone. As a person ages much of this marrow becomes fatty and ceases production. But it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.
It takes from 3 to 5 days for development of a reticulocyte from a hemocytoblast. Reticulocytes, immature rbc, move into the circulation and develop over a 1 to 2 day period into mature erythrocytes. About 1 to 2 % of rbc in the circulation are reticulocytes, and the exact percentage is a measure of the rate of erythropoiesis.
Functions
Manufacture - blood proteins - albumen, clotting proteins , urea - nitrogenous waste from amino acid metabolism , bile - excretory for the bile pigments, emulsification of fats by bile salts
Storage - glycogen , iron - as hemosiderin and ferritin , fat soluble vitamins A, D, E, K
Detoxification -alcohol , drugs and medicines , environmental toxins
Protein metabolism -
- transamination - removing the amine from one amino acid and using it to produce a different amino acid. The body can produce all but the essential amino acids; these must be included in the diet.
- deamination - removal of the amine group in order to catabolize the remaining keto acid. The amine group enters the blood as urea which is excreted through the kidneys.
Glycemic Regulation - the management of blood glucose.
- glycogenesis - the conversion of glucose into glycogen.
- glycogenolysis - the breakdown of glycogen into glucose.
gluconeogenesis - the manufacture of glucose from non carbohydrate sources, mostly protein
The small intestine
Digestion within the small intestine produces a mixture of disaccharides, peptides, fatty acids, and monoglycerides. The final digestion and absorption of these substances occurs in the villi, which line the inner surface of the small intestine.
This scanning electron micrograph (courtesy of Keith R. Porter) shows the villi carpeting the inner surface of the small intestine.
The crypts at the base of the villi contain stem cells that continuously divide by mitosis producing
- more stem cells
- cells that migrate up the surface of the villus while differentiating into
- columnar epithelial cells (the majority). They are responsible for digestion and absorption.
- goblet cells, which secrete mucus;
- endocrine cells, which secrete a variety of hormones;
- Paneth cells, which secrete antimicrobial peptides that sterilize the contents of the intestine.
All of these cells replace older cells that continuously die by apoptosis.
The villi increase the surface area of the small intestine to many times what it would be if it were simply a tube with smooth walls. In addition, the apical (exposed) surface of the epithelial cells of each villus is covered with microvilli (also known as a "brush border"). Thanks largely to these, the total surface area of the intestine is almost 200 square meters, about the size of the singles area of a tennis court and some 100 times the surface area of the exterior of the body.
Incorporated in the plasma membrane of the microvilli are a number of enzymes that complete digestion:
- aminopeptidases attack the amino terminal (N-terminal) of peptides producing amino acids.
- disaccharidasesThese enzymes convert disaccharides into their monosaccharide subunits.
- maltase hydrolyzes maltose into glucose.
- sucrase hydrolyzes sucrose (common table sugar) into glucose and fructose.
- lactase hydrolyzes lactose (milk sugar) into glucose and galactose.
Fructose simply diffuses into the villi, but both glucose and galactose are absorbed by active transport.
- fatty acids and monoglycerides. These become resynthesized into fats as they enter the cells of the villus. The resulting small droplets of fat are then discharged by exocytosis into the lymph vessels, called lacteals, draining the villi.
Contractility : Means ability of cardiac muscle to convert electrical energy of action potential into mechanical energy ( work).
The excitation- contraction coupling of cardiac muscle is similar to that of skeletal muscle , except the lack of motor nerve stimulation.
Cardiac muscle is a self-excited muscle , but the principles of contraction are the same . There are many rules that control the contractility of the cardiac muscles, which are:
1. All or none rule: due to the syncytial nature of the cardiac muscle.There are atrial syncytium and ventricular syncytium . This rule makes the heart an efficient pump.
2. Staircase phenomenon : means gradual increase in muscle contraction following rapidly repeated stimulation..
3. Starling`s law of the heart: The greater the initial length of cardiac muscle fiber , the greater the force of contraction. The initial length is determined by the degree of diastolic filling .The pericardium prevents overstretching of heart , and allows optimal increase in diastolic volume.
Thankful to this law , the heart is able to pump any amount of blood that it receives. But overstretching of cardiac muscle fibers may cause heart failure.
Factors affecting contractility ( inotropism)
I. Positive inotropic factors:
1. sympathetic stimulation: by increasing the permeability of sarcolemma to calcium.
2. moderate increase in temperature . This due to increase metabolism to increase ATP , decrease viscosity of myocardial structures, and increasing calcium influx.
3. Catecholamines , thyroid hormone, and glucagon hormones.
4. mild alkalosis
5. digitalis
6. Xanthines ( caffeine and theophylline )
II. Negative inotropic factors:
1. Parasympathetic stimulation : ( limited to atrial contraction)
2. Acidosis
3. Severe alkalosis
4. excessive warming and cooling .
5. Drugs ;like : Quinidine , Procainamide , and barbiturates .
6. Diphtheria and typhoid toxins.
The endocrine system along with the nervous system functions in the regulation of body activities. The nervous system acts through electrical impulses and neurotransmitters to cause muscle contraction and glandular secretion and interpretation of impulses. The endocrine system acts through chemical messengers called hormones that influence growth, development, and metabolic activities
Regulation of glomerular filtration :
1. Extrinsic regulation :
- Neural regulation : sympathetic and parasympathetic nervous system which causes vasoconstriction or vasodilation respectively .
- Humoral regulation : Vasoactive substances may affect the GFR , vasoconstrictive substances like endothelin ,Angiotensin II , Norepinephrine , prostaglandine F2 may constrict the afferent arteriole and thus decrease GFR , while the vasodilative agents like dopamine , NO , ANP , Prostaglandines E2 may dilate the afferent arteriole and thus increase the filtration rate .
2. Intrinsic regulation :
- Myogenic theory ( as in the intrinsic regulation of cardiac output) .
- Tubuloglomerular feedback: occurs by cells of the juxtaglomerular apparatus that is composed of specific cells of the distal tubules when it passes between afferent and efferent arterioles ( macula densa cells ) , these cells sense changes in flow inside the tubules and inform specific cells in the afferent arteriole (granular cells ) , the later secrete vasoactive substances that affect the diameter of the afferent arteriole.
Urine is a waste byproduct formed from excess water and metabolic waste molecules during the process of renal system filtration. The primary function of the renal system is to regulate blood volume and plasma osmolarity, and waste removal via urine is essentially a convenient way that the body performs many functions using one process. Urine formation occurs during three processes:
Filtration
Reabsorption
Secretion
Filtration
During filtration, blood enters the afferent arteriole and flows into the glomerulus where filterable blood components, such as water and nitrogenous waste, will move towards the inside of the glomerulus, and nonfilterable components, such as cells and serum albumins, will exit via the efferent arteriole. These filterable components accumulate in the glomerulus to form the glomerular filtrate.
Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo filtration; this is called the filtration fraction. The remaining 80% of the blood flows through the rest of the body to facilitate tissue perfusion and gas exchange.
Reabsorption
The next step is reabsorption, during which molecules and ions will be reabsorbed into the circulatory system. The fluid passes through the components of the nephron (the proximal/distal convoluted tubules, loop of Henle, the collecting duct) as water and ions are removed as the fluid osmolarity (ion concentration) changes. In the collecting duct, secretion will occur before the fluid leaves the ureter in the form of urine.
Secretion
During secretion some substances±such as hydrogen ions, creatinine, and drugs—will be removed from the blood through the peritubular capillary network into the collecting duct. The end product of all these processes is urine, which is essentially a collection of substances that has not been reabsorbed during glomerular filtration or tubular reabsorbtion.